CAMMS32400507: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, Study Two (CARE-MS SM II)

CAMMS32400507: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, Study Two (CARE-MS ^SMII)

Sponsored By:	Genzyme and Bayer Healthcare Pharma
Information Provided By:	Genzyme
ClinicalTrials.gov Identifier:	NCT00548405

The purpose of this study is to establish the efficacy and safety of two different doses of alemtuzumab as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with Rebif® (interferon beta-1a). The study will enroll patients who have received an adequate trial of disease-modifying therapies but continued to relapse while being treated, and who meet a minimum severity of disease as measured by MRI. Patients will have monthly blood tests and comprehensive testing every 3 months.

Condition	Intervention	Phase
Multiple Sclerosis, Relapsing-Remitting	Drug: low-dose (12 mg) alemtuzumab (Campath®/MabCampath®) Drug: high-dose (24 mg) alemtuzumab (Campath®/MabCampath®) Drug: interferon beta-1a (Rebif®)	Phase 3

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Official Title: A Phase 3 Randomized, Rater- and Dose-Blinded Study Comparing Two Annual Cycles of Intravenous Low- and High-Dose Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta-1a (Rebif®) in Patients With Relapsing-Remitting Multiple Sclerosis Who Have Relapsed on Therapy

Primary Outcome Measures:
Time to Sustained Accumulation of Disability (SAD) [Time Frame: 2 years]
Relapse Rate [Time Frame: 2 years]

Secondary Outcome Measures:
Proportion of patients who are relapse free at Year 2 [Time Frame: 2 years]
Change from baseline in EDSS [Time Frame: 2 years]
Acquisition of disability as measured by change from baseline in MSFC [Time Frame: 2 years]
Percent change from baseline in MRI-T2 hyperintense lesion volume at Year 2 [Time Frame: 2 years]

Every patient will receive active treatment; there is no placebo. Patients who qualify will be randomly assigned to treatment with either low-dose alemtuzumab, high-dose alemtuzumab, or Rebif® at a 2:2:1 ratio (ie, there is a 4-in-5 chance patients will be assigned to receive alemtuzumab treatment and a 1-in-5 change patients will be assigned to receive Rebif® treatment). Alemtuzumab will be administered in two annual cycles, once at the beginning of the study and again 1 year later. Rebif® will be self-injected 3 times per week for as long as the study continues. All patients will be required to return to their study site every 3 months for neurologic assessment. In addition, a safety-related blood test will be performed at least monthly. Participation in this study is estimated to last between 2 and 4 years; patients who receive alemtuzumab will be followed for at least 3 years after their last dose of alemtuzumab.

Diagnosis of MS and MRI scan demonstrating white matter lesions attributable to MS

Onset of MS symptoms within 5 years of screening

EDSS score 0.0 to 5.0

≥2 MS attacks (first episode or relapses) occurring in the 2 years prior to screening, with ≥1 attack in the 1 year prior to screening

≥6 months continuous treatment with beta interferon or glatiramer acetate during the past 5 years prior to screening.

≥1 MS attack (relapse) while receiving treatment with interferon beta or glatiramer acetate after being on that therapy for at least 6 months

Previous treatment with alemtuzumab or any other investigational drug for MS

Previous treatment with mitoxantrone or natalizumab

Exposure to immunosuppressive agents other than systemic corticosteroid treatment

Received treatment with a monoclonal antibody for any reason

Has any progressive form of MS

Any disability acquired from trauma or another illness that could interfere with evaluation of disability due to MS

Major systemic disease that cannot be treated or adequately controlled by therapy

Chronic infection with viral, mycobacterial or parasitic organisms

Autoimmune disorder (other than MS)

Impaired hepatic or renal function

History of malignancy (exception for basal cell skin carcinoma if disease-free for ≥5 years)

Medical, psychiatric, cognitive, or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study

Of childbearing potential with a positive serum pregnancy test

Current participation in another clinical study or previous participation in CAMMS323

Previous hypersensitivity reaction to other immunoglobulin product

Known allergy or intolerance to interferon beta, human albumin, or mannitol

Intolerance of pulsed corticosteroids, especially a history of steroid psychosis

Inability to self-administer subcutaneous (SC) injections or receive SC injections from caregiver

Inability to undergo MRI with gadolinium administration

Unwilling to use a reliable and acceptable contraceptive method throughout the study period (fertile patients only)

United States, Florida
Axiom Clinical Research of Florida, Tampa, Florida, United States; Recruiting
Neurological Associates, Pompano Beach, Florida, United States; Not yet recruiting
University of South Florida Medical Clinics, Tampa, Florida, United States; Recruiting

United States, Texas
Integra Clinical Research, L.L.C., San Antonio, Texas, United States; Recruiting
Neurology Center of San Antonio., San Antonio, Texas, United States; Recruiting
Central Texas Neurology Consultants, Round Rock, Texas, United States; Recruiting

United States, Colorado
Advanced Neurosciences Research LLC, Fort Collins, Colorado, United States; Recruiting

United States, Indiana
Fort Wayne Neurological Center, Fort Wayne, Indiana, United States; Recruiting

United States, Iowa
Ruan Neurology Clinical and Research Center, Des Moines, Iowa, United States; Recruiting

United States, Kentucky
Associates in Neurology, PSC, Lexington, Kentucky, United States; Recruiting

United States, Michigan
Michigan Medical, PC, Grand Rapids, Michigan, United States; Not yet recruiting

United States, Nevada
Nevada Neurological, Henderson, Nevada, United States; Not yet recruiting

United States, New York
MS Research Center of New York, New York, New York, United States; Recruiting

United States, Ohio
The Ohio State University Medical Center, Columbus, Ohio United States; Recruiting

United States, Virginia
MS Center of Greater Washington, Vienna, Virginia, United States; Recruiting

Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, Seaman S, Miller DH, Hale G, Waldmann H, Compston DA. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006 Jan;253(1):98-108. Epub 2005 Jul 27. : 16044212

Fox E, Sullivan H, Gazda S. Open label, single-arm, Phase II study of alemtuzumab in patients with active relapsing-remitting multiple sclerosis who have failed licensed beta-interferon therapies. Poster presentation P06.07 at the 59th Annual Meeting of the American Academy of Neurology (AAN) on 03 May 2007.

Study ID Numbers: CAMMS32400507
ClinicalTrials.gov Identifier: NCT00548405
Health Authority: United States: Food and Drug Administration; Canada: Health Canada; Australia: Department of Health and Ageing Therapeutic Goods Administration; Czech Republic: State Institute for Drug Control; Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products; Sweden: Medical Products Agency; United Kingdom: Medicines and Healthcare Products Regulatory Agency; France: Afssaps - French Health Products Safety Agency; Germany: Paul-Ehrlich-Institut; Russia: Ministry of Health and Social Development of the Russian Federation; Ukraine: State Pharmacological Center - Ministry of Health; Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica;Mexico: Federal Commission for Sanitary Risks Protection;

Brazil: National Health Surveillance Agency; Italy: The Italian Medicines Agency; Netherlands: Medical Ethics Review Committee (METC); Spain: Spanish Agency of Medicines; Belgium: Federal Agency for Medicinal Products and Health Products; Switzerland: Swissmedic